The major aim of this research is to learn about the cellular, and ultimately the molecular, interactions that govern the formation of orderly axonal connections in the mammalian visual system. The present research is centered around the general question of how the precise patterning of connectivity between the LGN and primary visual cortex is achieved during fetal and neonatal development in cat and ferret. Past work has shown that subplate neurons, an early-generated, transient cell type present throughout neocortical white matter, may play crucial roles in the sequence of steps that lead to the mature pattern of geniculocortical connections. Here, four sets of experiments are proposed to investigate this suggestion further: 1) The roles played by subplate neurons will be studied by deleting them selectively at three separate times in development. Consequences will be examined for initial pathway formation between LGN and cortex, for cortical target selection and ingrowth by LGN axons, and for the postnatal formation of ocular dominance columns. 2) The nature of the interactions between subplate neurons, LGN axons and the cortical neurons of layers 4 and 6 will be examined in vivo by investigating whether activity-dependent interactions are present and in vitro by studying connectivity between subplate neurons and layer 4 neurons using intracellular recordings and electron microscopy following biocytin injections in living cortical slices. Cocultures of LGN and cortex in vitro will also permit interactions and connectivity between LGN neurons, subplate neurons and layer 4 neurons to be investigated directly. 3) The factors affecting the survival and programmed death of subplate neurons will be studied by examining, both in vivo and in vitro, the effects of added neurotrophic factors (NGF BDNF and NT3) and by using in situ hybridization or Northern blots to determine their distribution in the fetal brain. 4) The development of the subplate in human postmortem material will be studied by examining changes in the pattern of immunostaining for a variety of antibodies against the neuronal or glial cytoskeleton, against synaptic vesicles, against growth cones, or against the NGF receptor. The results of these studies should aid in understanding not only how the visual system is wired up during development, but also since subplate neurons are present throughout the mammalian neocortex, should have general significance for mechanisms of cerebral cortical development. Moreover, recent experiments suggest that damage to subplate neurons in animals can have profound effects on the subsequent formation of thalamocortical connections. Since the subplate reaches its largest extent in the brain of the human fetus, it is possible that early damage there may underlie later neurological birth defects such as cerebral palsy or dyslexia.